LY243246 ((6S)-DDATHF), the 6S diastereomer of DDATHF, is a potent competitive inhibitor of 5’-phosphoribosylglycinamide formyltransferase (GAR transformylase). 6R- and 6S-diastereomers of DDATHF are remarkably similar and equiactive antimetabolites inhibitory to de novo purine synthesis[1].
Lometrexol hydrate (DDATHF hydrate), an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol hydrate can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol hydrate has anticancer activity[1][2].
Folinic acid is an adjuvant used in cancer chemotherapy involving the drug methotrexate.Target: AntifolateFolinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate), and, thus, has vitamin activity that is equivalent to that of folic acid. Since it does not require the action of dihydrofolate reductase for its conversion, its function as a vitamin is unaffected by inhibition of this enzyme by drugs such as methotrexate. In 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate exists. Although the mechanism is not very clear, the polyglutamylation of methotrexate and dihydrofolate in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folinic acid in normal cells [1]. Folinic acid is generally administered along with MTX as a rescue agent to decrease MTX-induced toxicity. However, information regarding the inhibitory effect of folinic acid against cytogenetic damage caused by MTX is limited. This study was conducted to assess the cytogenetic effect of MTX and its inhibition by folinic acid (FA) using the micronucleus and chromosomal aberration assays concurrently [2].
10-Methyl-10-deazaaminopterin is a folate analog and an antifolate. 10-Methyl-10-deazaaminopterin can be used for the research of cancer[1].
Trimethoprim sulfate is a bacteriostatic antibiotic and an orally active dihydrofolate reductase inhibitor. Trimethoprim sulfate is active against a wide range of Gram-positive and Gram-negative aerobic bacteria. Trimethoprim sulfate has the potential for the research of urinary tract infections, Shigellosis and Pneumocystis pneumonia. Trimethoprim sulfate can inhibit infection of Influenza A virus in chick embryo when combinated with zinc[1][2][3][4].
Pemetrexed-d5 is the deuterium labeled Pemetrexed[1]. Pemetrexed (LY231514) is an antifolate, the Ki values of the pentaglutamate of Pemetrexed (LY231514) are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively[2].
Pemetrexed is a novel antifolate, the Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively.
Methotrexate-d3 (Amethopterin-d3) is the deuterium labeled Methotrexate. Methotrexate (Amethopterin), an antimetabolite and antifolate agent, inhibits the enzyme dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibiting DNA synthesis. Methotrexate, also an immunosuppressant and antineoplastic agent, is used for the research of rheumatoid arthritis and a number of different cancers (such as acute lymphoblastic leukemia)[1][2][3].
Trimetrexate trihydrochloride is a antibiotic, also a potent dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC50 values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate trihydrochloride can be used for researching Pneumocystis carinii pneumonia (PCP)[1][2].
Levomefolate is an artificial form of folate.IC50 Value:Target: AntifolateThe calcium salt of L-5-methyltetrahydrofolic acid which belongs to the group of folate vitamins (Vitamin B9, Folacin). It is a coenzymated form of folic acid and a more bioavailable alternative in dietary supplements.
LY 254155, an antifolate, inhibits hGARFT and binds to mFBP with Kis of 2.1±0.2 and 1.7±0.1 nM, respectively.
Pyrimethamine(RP4753) is a medication used for protozoal infections; interferes with tetrahydrofolic acid synthesis from folic acid by inhibiting the enzyme dihydrofolate reductase (DHFR).IC50 Value: 15.4 nM (Plasmodium falciparum) [1]Target: DHFR; antifolatein vitro: Three susceptibility levels (susceptible, intermediate, and resistant) were observed in the response of culture-adapted clones and strains to pyrimethamine (50% inhibitory concentration [IC50]) < 100, 100-2,000, and > 2,000 nM) and cycloguanil (IC50 < 50, 50-500, and > 500 nM). Based on these susceptibility levels, 73 and 68 of 96 fresh clinical isolates were susceptible to pyrimethamine (mean IC50 15.4 nM) and cycloguanil (mean IC50 11.1 nM), respectively [1]. We tested pyrimethamine(previously reported to suppress SOD1 expression), several compounds currently in trials in human and murine ALS, and a set of 1040 FDA-approved compounds. In a PC12 cell-based assay, no compounds reduced SOD1 promoter activity without concomitant cytotoxicity. Additionally,pyrimethamine failed to repress levels of SOD1 protein in HeLa cells or homogenates of liver, spinal cord and brain of wild-type mice [3].in vivo: (131)I-Pyrimethamine (specific activity: 7.08 MBq/ mol) was injected intravenously into the tail vein of the control and infected rats. Static whole body images of the rats were acquired under the gamma camera at 5 min, 45 min, 2 h, 6 h, and 24 h following the intravenous administration of the radioactivity (3.7 MBq/rat) [2]. The 10-day treatment with 10mg/kg/day of fluconazole combined with 40/1mg/kg/day sulfadiazine and pyrimethamine resulted in 93% survival of CF1 mice acutely infected with the highly virulent T. gondii RH strain, versus 36% of mice treated with just sulfadiazine and pyrimethamine [4].Toxicity: Sulfadoxine/pyrimethamine is well tolerated as treatment and when used as intermittent preventive treatment in pregnant African women. Sulfadoxine/pyrimethamine is no longer used as prophylaxis because it may cause toxic epidermal necrolysis and Stevens Johnson syndrome [5].
Methotrexate metabolite (DAMPA), the active metabolite of Methotrexate. Methotrexate is a folic acid antagonist that is widely used as an immunosuppressant and chemotherapeutic agent[1].
Trimetrexate (CI-898) isethionate is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC50 values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate isethionate can also inhibit the growth of various cancer cells. Trimetrexate isethionate can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer[1][2][3][4][5].
Trimethoprim hydrochloride is a bacteriostatic antibiotic and an orally active dihydrofolate reductase inhibitor. Trimethoprim hydrochloride is active against a wide range of Gram-positive and Gram-negative aerobic bacteria. Trimethoprim hydrochloride has the potential for the research of urinary tract infections, Shigellosis and Pneumocystis pneumonia. Trimethoprim hydrochloride can inhibit infection of Influenza A virus in chick embryo when combinated with zinc[1][2][3][4].
EC0488 is used to synthesize EC0531 with folate receptor (FR)-specific and anti-tumor activities[1].
DHFR-IN-2 (compound 4e) is a potent and uncompetitive inhibitor for MtDHFR (dihydrofolate reductase from M. tuberculosis), with an IC50 of 7 μM. DHFR-IN-2 can be used for tuberculosis (TB) research[1].
Levomefolic acid (5-MTHF) is the natural, active form of folic acid used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine among other functions. IC50 value: Target: Folate analogLevomefolic acid has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancers. Levomefolic acid (5-MTHF) has the prominent antioxidant activity. A high dose of 5-MTHF or folic acid does not influence Natural killer (NK) cell function in vitro.
Pemetrexed disodium is a novel antifolate that inhibits the folatedependent enzymes thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase with Kis of 1.3, 7.2, and 65 nM, respectively.
Edatrexate (CGP 30694), as known as 10-Ethyl-10-deazaaminopterin, is Methotrexate (HY-14519) analog, exhibits antitumor activity against MTX-resistant tumors. Edatrexate is an antifolate antimetabolite, can be used for reasearch of non-small-cell lung cancer, breast cancer, non-Hodgkin's lymphoma, and cancer of the head and neck[1][2].
Talotrexin (PT523), an analog of Aminopterin (HY-14518), is a nonpolyglutamatable classic antifolate. Talotrexin is a RFC (reduced folate carrier) specific inhibitor and selectively inhibits RFC transport. Talotrexin shows antitumor activity by targeting DHFR to inhibit tumor growth[1][2].
10-Formylfolic acid is a potent inhibitor of dihydrofolate reductase. 10-Formylfolic acid be used as an early indicator of leukemia[1][2].
Lometrexol (DDATHF), an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) by tightly binding with it. Lometrexol can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol has anticancer activity[1].
LY309887 is a potent inhibitor of glycinamide ribonucleotide formyltransferase (GARFT), with a Ki of 6.5 nM, and has antitumor activity.
DHFR-IN-3 is a dihydrofolate reductase (DHFR) inhibitor with the IC50 values of 19 μM and 12 μM in rat liver and P. carinii DHFR, respectively[1].
Pralatrexate(Folotyn) is an antifolate, and structurally a folate analog. Its IC50 is < 300 nM in some cell lines.IC50 Value: < 300 nMTarget: AntifolatePralatrexate is an antifolate (a folate analogue metabolic inhibitor) designed to accumulate preferentially in cancer cells. Based on preclinical studies, researchers believe that Pralatrexate selectively enters cells expressing reduced folate carrier type 1 (RFC-1), a protein that is overexpressed on certain cancer cells compared to normal cells.
Ketotrexate sodium is an orally active antifolate and immunosuppressant. Ketotrexate sodium has good anti-inflammatory activity and is widely used in rheumatoid arthritis (RA). Ketotrexate sodium is used in research into cancer and autoimmune diseases[1][2].
Proguanil-d4 is the deuterium labeled Proguanil[1]. Proguanil, an antimalarial prodrug, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil is a dihydrofolate reductase (DHFR) inhibitor[2][3].
Proguanil hydrochloride, an antimalarial prodrug, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is a dihydrofolate reductase (DHFR) inhibitor[1][2].
Pemetrexed disodium hemipenta hydrate is a novel antifolate, the Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively.